Studies were performed to investigate the role of macrophages against tumor cells in vivo and to compare the contribution of these cells to that of natural killer (NK) cells. Animals inoculated with Brewer's thioglycollate-elicited macrophages 2 days before to 15 minutes after iv inoculated of B16 tumor cells, had reduced clearance of the tumor cells and developed a greater number of metastases. Animals treated with antibody to asialo GM1 had reduced NK activity and a greater number of metastases. Adoptive transfer of activated macrophages reduced the number of metastases in anti-asialo GM1-treated mice. Studies of the homing of adoptively transferred macrophages indicated that the traffic pattern of these cells is in part dictated by the type of agent used to elicit the peritoneal macrophages. Two new monoclonal antibodies have been developed that are specific for macrophages. Both recognize antigens that are found on thioglycollate-elicited cells and on cultured macrophages from bone marrow but are weakly expressed on resident and peptone-elicited macrophages. Plasminogen activator production has been used as an indicator for activation with macrophages treated with macrophage activation factor (MAF) but there is not a positive correlation with macrophages activated by endotoxin. T cell hybrids producing MAF have been developed from Ly 1+ 2+ and Ly 1+ 2- enriched populations of T cells.